Military Strategies for Sustainment of Nutrition and Immune Function in the Field (1999) / Chapter Skim
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1 A Review of the Role of Nutrition in Immune Function
1 A Review of the Role of Nutrition in Immune Function
Pages 19-98
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From page 19... ...
Combined stressors may reduce the normal ability of soldiers to resist pathogens, may increase their susceptibility to biological agents employed against them, and may reduce the effectiveness of vaccines intended to protect them. Military studies in multistressor environments have demonstrated that higher energy intakes will better sustain the indices of immune status.
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From page 20... ...
Army Basic Combat Training, and a review of the results of a nutrition intervention project conducted during a 1992 U.S. Army Ranger training class.
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From page 21... ...
Friedl in Chapter 4, studies in multistressor environments, such as basic training and the Special Forces' Assessment and Selection Course (SEAS) , demonstrated that higher energy intakes were better able to sustain the indices of immune status.
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Currently, U.S. Ranger training consists of three 3-week phases conducted at widely varying sites with differing physical demands: military base training, mountain training, and swamp training.
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From page 23... ...
The stressors faced by military personnel include altered environments (heat or cold, varying altitudes and terrains) , excessive work loads, alterations in nutrient intake, and possible exposure to new pathogens and/or chemical toxins.
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24 Cal C)
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25 As .s 3 ¢ o Cal A V V, C)
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26 x .~ s EM Cal A ¢ ~ V o Ct o v a: _ '_ ~o 1 1~ o _ ~ _ 1 ° ~1 _ U, C)
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A number of investigations have grown out of the use of the Ranger training model. These studies established a relationship between energy deficit (as rate of weight loss)
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Fairbrother arid T.R. Kramer, Unpublished data, USARIEM, Natick, Mass., 1993~; BCT, 1993 Anny Basic Combat Training (Westphal et al., 1995~.
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From page 29... ...
Army Ranger Training Brigade and SEAS. These studies were designed to test proposed guidelines for sleep deprivation, food restriction, and environmental exposure, with immune response as one of the variables of concern.
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From page 30... ...
Evaluation of the effect of a carbohydrate-electrolyte beverage on performance showed no significant effect on lymphocyte proliferation; however, the study involved more-than-adequate energy intakes (4,890-7,846 kcal/d) and was probably not directly applicable to the field situation (Montain et al., 1995~.
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From page 31... ...
Changes in specific immune parameters documented during these training periods show a general decline in immune function, similar to that seen in response to strenuous exercise (see Table 1-3~. In these troops, an increase in energy intake of 1,200 kcal/d appeared to have little effect on modulating the overall immune response to exercise.
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32 Cal CQ ._ C)
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33 ~V, corn ~ Cal _ do V 11 m ~ lo: S Cal O so 11 z SO C)
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The immune response seen in U.S. Ranger studies is similar in most respects to that observed in the Norwegian training.
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. · Restoration of energy requirements over the long run can improve the composition of weight loss dramatically, influencing immune function less severely.
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From page 36... ...
Dose-response curves should form the basis of recommendations for optimal nutrient intake. Immune responses provide sensitive and functional indices of nutritional status and can aid in assessing prognosis in medical and surgical patients.
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From page 37... ...
For example, the reduced immunologic response in elderly subjects pre- and postbereavement is an example of emotional stress that may interact with nutritional or other factors to reduce immune responses. Moderate, graded exercise in elderly subjects has been shown to enhance immune responses and decrease the incidence of infection.
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38 / it at as CO A= cn C~Z \ ~ =° ~ ~ _ ~ zig a,$ ~ \ .: (~_ ~.o ~ of , ._ Hi ~ C)
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From page 39... ...
enumerates the most significant characteristics of cytokines: multiple biologic activities (pleiotropy; for example, IL-1 exhibits more than 50 unique and separate functions) , redundancy of actions (for example, IL-1, IL-6, and tumor necrosis factor [TNF]
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Stress and glucocorticoid responses during stress are important regulators of cytokine production, tending to shift immune responses from T-helper 1 (Thl) to Th2-type responses (cellular to humoral)
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41 ~ mu.
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42 C it)
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Assessment Techniques There is no criterion test for immune deficiency. Many existing indicators such as lymphocyte proliferation assays tend to be poor predictors of disease attributable to immune deficiency (Straight et al., 1994~.
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An additional problem is that recovery (defined by Cunningham-Rundles as the ability to recover from a threat to the immune system) may be the most critical parameter for assessing the likely response to future immune exposure but may not be predictable based on the magnitude of the immune response in a test situation.
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From page 45... ...
. Cunningham-Rundles' recommendations include the need to document the type and range of alterations in immune function expected under typical training conditions, followed by careful design of studies allowing assessment at several levels of immune response.
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From page 46... ...
In summary, the design of an immune function assessment study is a significant challenge. According to Cunningham-Rundles and others, population research must move in the direction of identifying correlations among changes in individual parameters of immune function and patterns of immune responses, imposition of specific stressors, and disease outcome.
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From page 47... ...
Protein and Amino Acids Protein deficiency is consistently observed to interfere with maintaining resistance to infection because most immune mechanisms are dependent on cell replication or the production of active protein compounds. As might be expected, deficiencies of essential amino acids can result in an altered humoral response, whereas deficiencies of single nonessential amino acids may have little effect on the immune system, although there are some exceptions.
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From page 50... ...
Over the past decade, glutamine has been studied for its ability to promote immune cell proliferation and enhance immune function. Glutamine appears to promote lymphocyte proliferation and macrophage phagocytosis (Parry-Billings et al., 1990)
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From page 51... ...
A hallmark of vitamin A deficiency is depressed antibody responses to T-cell-dependent and independent antigens, which may be mediated by alterations in the production of some cytokines. However, some viral infections do not reduce and may increase immunoglobulin G response, which may reduce or otherwise alter other immune responses (Ross and Stephenson, 19963.
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From page 52... ...
The predominant physiologic function of vitamin E is in its role as an antioxidant required for the protection of cellular as well as membrane polyunsaturated fatty acids. Vitamin E also protects membrane-bound nucleic acids and thiol-rich proteins from oxidative damage.
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From page 53... ...
, and IL-2 production in a group of healthy elderly subjects receiving 800 IU of vitamin E daily for 30 days. The authors therefore believe that vitamin E supplements act to improve the immune response by decreasing the production of PGE2, which in turn moderates cyclooxygenase activity.
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From page 54... ...
Vitamins C and E are both powerful antioxidants, have been shown to enhance the immune response, and are relatively nontoxic. There is considerable evidence regarding the possible benefits of vitamin E and C supplementation in terms of reducing oxidative stress and/or damage during exercise.
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From page 55... ...
to varying degrees, depending on structure, amounts, and ratios. Fatty acids affect immune function not only by the total amount of fat present, but also by the amounts of and ratio between the n-6 and n-3 types of PUPA that act primarily through prostaglandins and leukotriene production and activity, as depicted in Figure 1-4.
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From page 56... ...
Depending on their concentration and type, prostaglandins and leukotrienes stimulate or inhibit the activity of immune cells. Other 20-carbon fatty acids compete with arachidonic acid for the lipoxygenase and cyclooxygenase enzymes and reduce the products formed from arachidonic acid, including eicosanoids of the 2-series and leukotriene B4, which are potent modulators of the immune cell: PGE1, PGI2, PGI3, and PGE2, prostaglandins E1, I2, Is, and E2, respectively.
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From page 57... ...
diet are vegetable oils. Clinical and experimental studies have demonstrated that the structural and functional properties of immune cells can be modified by dietary supplementation with n-3 PUFAs from fish oil or linolenic acid, and in vivo tests are the most appropriate approach for determining the effect of different dietary fatty acids on immune function and inflammation, but few studies have been reported in humans (Carder, 1998~.
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From page 58... ...
(1996) used a crossover study design in which healthy men were fed a baseline diet containing 30 percent of energy as fat (with equal amounts of saturated fatty acids, monounsaturated fatty acids, and PUFAs)
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From page 59... ...
Calder (1997) has suggested that diets enriched in fish oil n-3 PUFAs may be of use in the therapy of acute and chronic inflammation and disorders involving inappropriately active immune responses (such as autoimmune disorders)
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From page 60... ...
Iron influences immune functions via cytokines and nitric oxide (Weiss et al., 1995) , and iron-containing enzymes play a key role in the bactericidal activities of phagocytic cells.
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Whether iron deficiency affects the host-pathogen relationship at the clinical level remains to be demonstrated conclusively. However, as discussed below, it is clear that iron deficiency does not and will not enhance immune responses.
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From page 62... ...
, when the criterion for iron deficiency was defined as a serum ferritin concentration of less than 12 ,ug/L and the criteria for iron deficiency anemia were defined as a combination of low serum ferritin and a hemoglobin concentration of less than 120 g/L, 17 percent of new female recruits who were tested at entry to BCT fit the criteria for iron deficiency while 8 percent could be classified as having iron deficiency anemia. A survey of a similar (but not the same)
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From page 63... ...
Iron deficiency anemia can be expected to have adverse effects on military performance of both men and women depending in part on its severity. Performance deficits in both men and women due to compromised iron status have been demonstrated most clearly during exercise of prolonged duration such as long-distance running (Newhouse and Clement, 1988~.
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From page 64... ...
There is some evidence to suggest that the interactive effects of zinc and copper on the immune response may involve differential cytokine stimulation (Scuderi, 1990~. In studies with children, zinc has been shown to reduce the morbidity associated with secretory diarrhea (Rosado et al., 1997; Sazawal et al., 1995~.
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From page 65... ...
Many of selenium's effects can be explained most simply on the basis that it is a required constituent of the glutathione peroxidase family of enzymes. Selenium deficiency has been associated with an increased susceptibility to certain infectious pathogens, perhaps because of decreased antibody production and impaired lymphoproliferative responses in the deficient state (KiremidjianSchumacher and Stotzky, 1987~.
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From page 66... ...
can be explained most readily on the basis of an increased oxidative stress imposed on the host by the diet. The biochemical mechanisms responsible for these dietary effects on viral virulence in mice are not known, but defects in certain host immune functions were observed (impaired mitogen- and antigen-stimulated T-cell proliferation)
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From page 67... ...
Reichlin describes the hypothalamic-pituitary-adrenal, thyroid, and gonadal system interrelationships and responses to inflammatory disease conditions, whereas Kapcala discusses the involvement of individual cytokines in stimulating the hypothalamicpituitary-adrenal axis. Superimposed on the demands of exercise and neurohormonal or neuroimmunological activation, an individual's innate biologic rhythms also may affect changes in the body's immune response, as described by Erhard Haus in Chapter 20.
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From page 68... ...
In the elderly, intense physical training is associated with an increase in NK- and T-cell activity (Shinkai et al., 1995) and PHA-induced lymphocyte proliferation (Nieman et al., 1993b)
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From page 69... ...
Low energy intake, weight reduction, and increased levels of circulating glucocorticoids often associated with field maneuvers (see Shippee and Wiik, Chapters 5 and 6, respectively) may suppress the immune system independently, and superimposing physical activity may increase vulnerability.
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From page 70... ...
in a rather stereotypic manner by elaborating "stress hormones." All of the hormones that regulate carbohydrate metabolism participate in host responses to infection. Among these are the glucocorticoids from the adrenal cortex, the catecholamines from the adrenal medulla and sympathetic nervous system, and glucagon, a pancreatic hormone.
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From page 71... ...
Since almost all components of the immune response are inhibited by cortisol and other glucocorticoids, pituitary-adrenal activation is accompanied by a reduction in the intensity of the immune response (Kapcala, 1997; Reichlin 1993) (Figure 1 -51.
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From page 72... ...
VP, CRH neurons are in turn subject to a wide range of influencescirculating cytokines, prostaglandins, and many neurotransmitters. Some, such as acetylcholine (ACH)
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From page 73... ...
, and IGF-I enhances the immune response in rats (Hinton et al., 1995~. In summary, a variety of changes in the hypothalamic-pituitary system occur via activation of inflammatory responses (and cytokine release)
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From page 74... ...
to influence CRH (see Kapcala, Chapter 19~. This communication also may occur via circulating cytokines that can activate peripheral sensory neurons, relaying input to the brain, which ultimately stimulates CRH neurons (Wan et al., 1994; Watkins et al., 1995~.
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From page 75... ...
pattern of functioning of the cells in the immune system can have detrimental consequences. Circaseptan rhythms also have been observed in immune responses.
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From page 76... ...
are found In the serum of healthy individuals. For example, serum concentrations of IL-6, which plays an important role in host defense mechanisms, inflammation, and immune responses, are highest during the night and lowest at midmorning (10:00 a.m.)
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From page 77... ...
Moreover, circannual rhythms in serum immunoglobulins, with peak concentrations during mid-summer to midautumn, have been reported in healthy human subjects. Potential Clinical Relevance of Biologic Rhythms in Immune Function Human immune responses to inoculation may vary as a function of the time of day at which an antigen is introduced.
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From page 78... ...
Impairments in immune function also have been noted in shift workers and individuals suffering from "jet lag." However, because shift work and jet lag are frequently associated with some degree of sleep deprivation, it is not known whether the alterations in immune function observed in these situations are primarily a consequence of sleep deprivation or of circadian desynchronization. Circadian rhythms in immune function also are influenced by levels of physical activity and patterns of food intake.
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From page 79... ...
Many of these rhythms are inherited; however, others are adjusted in response to environmental variables such as light~ark cycles, environmental temperature, social situation, exercise, and food intake. Because military personnel may encounter infectious agents during field operations and can be subjected to extremes of environmental factors (for example, extreme heat or cold, intense physical exercise, sleep deprivation, and limited times for food consumption)
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From page 80... ...
These changes are believed to be associated with the early stage of HAPE and possibly with pulmonary hypertension; however it is not clear how the ability of the immune system to respond to infectious agents is affected. Sleep Deprivation The influence of sleep deprivation on immune Function was mentioned earlier as a factor in the decreased immune response observed in the Ranger studies.
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From page 81... ...
The advantages and disadvantages of vitamin and mineral supplementation have been considered not only for their effects on immune system function, but for overall health in general. Finally, the physiologic and immune responses to alterations in neuroendocrine function are examined in depth.
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From page 82... ...
1981. Arginine stimulates lymphocyte immune response in healthy human beings.
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From page 83... ...
1987. The effect of copper deficiency on the immune response in mice.
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From page 84... ...
1998. Autonomic, neuroendocrine, and immune responses to psychological stress: the reactivity hypothesis.
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From page 85... ...
1982. Excessive intake of zinc impairs immune response.
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From page 86... ...
1989. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells.
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From page 87... ...
1995. Insulinlike growth factor-I enhances immune response in dexamethasone-treated or surgically stressed rats maintained with total parenteral nutrition.
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From page 88... ...
Anny Ranger Training Class 11/91. A brief report of the Committee on Military Nutrition Research, Food and Nutrition Board.
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From page 89... ...
l9B7. Selenium and immune responses.
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From page 90... ...
1990. Immune response in copper deficiency.
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From page 91... ...
1991. Dietary supplementation with omega-3-polyunsaturated fatty acids decreases mononuclear cell proliferation and interleukin-l,B content but not monokine secretion in healthy and insulin-dependent diabetic individuals.
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From page 92... ...
1996. Immune response to obesity and moderate weight loss.
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From page 93... ...
1997. Cyclic vs continuous enteral feeding with omega-3 and gamma-linolenic fatty acids: effects on modulation of phospholipid fatty acids in rat lung and liver immune cells.
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From page 94... ...
1990. Decreased lymphocyte subsets and K-cell activity in iron deficiency anemia.
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From page 95... ...
A report of the Committee on Military Nutrition Research, Food and Nutrition Board, Institute of Medicine. Washington, D.C.: National Academy Press.
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From page 96... ...
1996. Granulocyte chemiluminescence response to serum opsonized particles ex vivo during long-term strenuous exercise, energy, and sleep deprivation in humans.
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From page 97... ...
1989. Differential regulation of lipopolysaccharide-induced interleukin-1 and tumor necrosis factor synthesis: Effects of endogenous and exogenous glucocorticoids and the role of the pituitary-adrenal axis.
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